1. Field of the Invention
The present invention relates to an improved process for preparing vinyl imidazole derivatives (I) which can be utilized as antimycotic agents for humans and animals or agricultural fungicides, and furthermore, it also relates to an improved method of production of useful monoimidazole derivatives (II). The monoimidazole derivatives are useful as intermediates for preparing the vinyl imizadole derivatives.
Specifically, the present invention relates to a method of preparation of compounds of the formula: ##STR2## wherein R.sup.1 is halogen, and R.sup.2, X, and Y are each hydrogen or halogen.
2. Prior Art
(1) For example, the compounds (I) have been prepared by reacting 2-[1-(1H-imidazol-1-yl)vinyl]phenols with mono- or di-(halo-substituted)benzyl halogenide in the presence of a base such as sodium hydride in dried dimethylformamide (hereinafter referred to as "DMF") [U.S. Pat. No. 4,328,348].
(2) The monoimidazole derivatives (II), i.e., 2-[1-(1H-imidazol-1-yl)vinyl]phenols have been prepared by reacting o-hydroxyacetophenones (III) with 1,1'-thionyl diimidazole [U.S. Pat. No. 4,328,348], according to the following scheme: ##STR3## wherein Hal is halogen, and R.sup.1, R.sup.2, X, and Y are each as defined above. In the prior art, the following problems still remain.
(i) Referring to the reaction for producing the compounds (I), (a) sodium hydride used as a base is expensive and extremely dangerous during the operation; (b) dried DMF as a solvent is easily decomposed in a base and difficult to effectively recover; (c) certain decomposed compounds from DMF may react with mono- or di-(halo-substituted)benzyl halogenide to give some by-products; and (d) the objective compound (I) is obtained in low yield because of the difficulty of separating the by-products therefrom. PA1 (ii) In reference to the reaction for producing the monoimidazole derivatives (II), (a) a large amount of a 1H-imidazole (usually more than 2 mole equivalent) has to be used in the preparation of 1,1'-thionyl diimidazole which reacts with an o-hydroxyacetophenone (III); (b) the diimidazole compound (IV) of the formula: ##STR4## wherein X and Y are each hydrogen or halogen is produced as a by-product in addition to the monoimidazole compound (II); and (c) therefore, the yield of the compound (II) is low and it has to be separated from the by-product (IV) by purification.
The present inventors have succeeded in solving the above problems (i) and (ii).
Referring to the problem (i), the present inventors have used safer and less expensive alkali metal hydroxide instead of sodium hydride; and they also found that dimethylamine resulting from the decomposition of DMF sometimes reacts with 4-chlorobenzyl bromide to give (4-chlorobenzyl)dimethylamine as a by-product and that a solvent containing dimethylsulfoxide can be used in place of DMF for avoiding the production of the (4-chlorobenzyl)dimethylamine to afford the vinyl imidazole derivatives (I) in high yield.
Regarding the problem (ii) the present inventors have found that half the amount of 1H-imidazole in the reaction medium is consumed in the production of 1,1'-thionyl diimidazole, that another half works as a base; and that the base can be replaced by other less expensive ones.
Furthermore, the present inventors have found that 1-halosulfinyl-1H-imidazole can be used in place of 1,1'-thionyl diimidazole prepared by reacting thionyl chloride with a 2 equimolar amount of 1H-imidazole.
Additionally, the present inventors have developed a process for converting a diimidazole (IV) into a monoimidazole (II) to increase the yield of the monoimidazole (II).